We propose that the sudden infant death syndrome (SIDS) results when an infant when a neuronal vulnerability is exposed to an exogenous stressor at a critical time in development. The arcuate nucleus in humans, and homologous structures in the piglet- the retrotrapezoid nucleus, parapyramidal neurons, caudal raphe and chemoreceptor regions along the rostral and caudal surface of the ventral medulla-are possible sites of neuronal vulnerability. The exogenous stressor may be stimulation of facial or upper airway receptors or compression of the chest. These exogenous stressors inhibit respiration and may promote cardiovascular instability, but normal protective responses arising from asphyxia (hypoxia and hypercapnia) oppose the effect of these stressors, increase breathing, stabilize blood pressure, promote arousal, which alleviates inhibitory influences on respiration and may lead to postural changes that relieve asphyxia. Disruption of the arcuate neurons or the piglet homologue diminishes or eliminates protective responses, permits the unfettered actions of stimuli inhibiting respiration and may make a fatal outcome more likely. Specific Aim 1: In the decerebrate piglet at different developmental ages, we will examine the effect of lesions in the piglet homologue of the arcuate nucleus on ventilatory and cardiovascular responses (phrenic nerve activity, heart rate and blood pressure) during stimulation of the trigeminal or superior laryngeal nerve or stimulation of a now intercostal nerve during hypercapnia or hypoxia. Specific Aim 2: In decerebrate piglets at the developmental age most susceptible to disruption of protective responses we will examine the role of muscarinic, ionotropic glutamate and thyrotropin releasing hormone receptors in brainstem regions homologous to the arcuate nucleus on ventilatory and cardiovascular responses as in Specific Aim 1. Specific Aim 3: We will examine the effect of chronic lesions in the homologue of the arcuate nucleus on ventilatory and cardiovascular responses during stimulation of the trigeminal, superior laryngeal and intercostal nerves in unanesthetized piglets during room air exposure, hypercapnia or hypoxia during wakefulness and sleep (NREM and REM).